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Cerebral Ischemia Is Exacerbated by Extracellular Nicotinamide Phosphoribosyltransferase via a Non-Enzymatic Mechanism

Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT) is not clear. Here we show that eNAMPT protein level was elevated in the ischem...

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Autores principales: Zhao, Bing, Zhang, Meng, Han, Xue, Zhang, Xia-Yan, Xing, Qiong, Dong, Xu, Shi, Qiao-Juan, Huang, Peng, Lu, Yun-Bi, Wei, Er-Qing, Xia, Qiang, Zhang, Wei-Ping, Tang, Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877362/
https://www.ncbi.nlm.nih.gov/pubmed/24392007
http://dx.doi.org/10.1371/journal.pone.0085403
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author Zhao, Bing
Zhang, Meng
Han, Xue
Zhang, Xia-Yan
Xing, Qiong
Dong, Xu
Shi, Qiao-Juan
Huang, Peng
Lu, Yun-Bi
Wei, Er-Qing
Xia, Qiang
Zhang, Wei-Ping
Tang, Chun
author_facet Zhao, Bing
Zhang, Meng
Han, Xue
Zhang, Xia-Yan
Xing, Qiong
Dong, Xu
Shi, Qiao-Juan
Huang, Peng
Lu, Yun-Bi
Wei, Er-Qing
Xia, Qiang
Zhang, Wei-Ping
Tang, Chun
author_sort Zhao, Bing
collection PubMed
description Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT) is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO) and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD) induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture. In the mixed culture, NAMPT protein promoted TNF-α release in a time- and concentration-dependent fashion, while TNF-α neutralizing antibody protected OGD-induced, NAMPT-enhanced neuronal injury. Importantly, H247A mutant of NAMPT with essentially no enzymatic activity exerted similar effects on ischemic neuronal injury and TNF-α release as the wild type protein. Thus, eNAMPT is an injurious and inflammatory factor in cerebral ischemia and aggravates ischemic neuronal injury by triggering TNF-α release from glia cells, via a mechanism not related to NAMPT enzymatic activity.
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spelling pubmed-38773622014-01-03 Cerebral Ischemia Is Exacerbated by Extracellular Nicotinamide Phosphoribosyltransferase via a Non-Enzymatic Mechanism Zhao, Bing Zhang, Meng Han, Xue Zhang, Xia-Yan Xing, Qiong Dong, Xu Shi, Qiao-Juan Huang, Peng Lu, Yun-Bi Wei, Er-Qing Xia, Qiang Zhang, Wei-Ping Tang, Chun PLoS One Research Article Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT) is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO) and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD) induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture. In the mixed culture, NAMPT protein promoted TNF-α release in a time- and concentration-dependent fashion, while TNF-α neutralizing antibody protected OGD-induced, NAMPT-enhanced neuronal injury. Importantly, H247A mutant of NAMPT with essentially no enzymatic activity exerted similar effects on ischemic neuronal injury and TNF-α release as the wild type protein. Thus, eNAMPT is an injurious and inflammatory factor in cerebral ischemia and aggravates ischemic neuronal injury by triggering TNF-α release from glia cells, via a mechanism not related to NAMPT enzymatic activity. Public Library of Science 2013-12-31 /pmc/articles/PMC3877362/ /pubmed/24392007 http://dx.doi.org/10.1371/journal.pone.0085403 Text en © 2013 Zhao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhao, Bing
Zhang, Meng
Han, Xue
Zhang, Xia-Yan
Xing, Qiong
Dong, Xu
Shi, Qiao-Juan
Huang, Peng
Lu, Yun-Bi
Wei, Er-Qing
Xia, Qiang
Zhang, Wei-Ping
Tang, Chun
Cerebral Ischemia Is Exacerbated by Extracellular Nicotinamide Phosphoribosyltransferase via a Non-Enzymatic Mechanism
title Cerebral Ischemia Is Exacerbated by Extracellular Nicotinamide Phosphoribosyltransferase via a Non-Enzymatic Mechanism
title_full Cerebral Ischemia Is Exacerbated by Extracellular Nicotinamide Phosphoribosyltransferase via a Non-Enzymatic Mechanism
title_fullStr Cerebral Ischemia Is Exacerbated by Extracellular Nicotinamide Phosphoribosyltransferase via a Non-Enzymatic Mechanism
title_full_unstemmed Cerebral Ischemia Is Exacerbated by Extracellular Nicotinamide Phosphoribosyltransferase via a Non-Enzymatic Mechanism
title_short Cerebral Ischemia Is Exacerbated by Extracellular Nicotinamide Phosphoribosyltransferase via a Non-Enzymatic Mechanism
title_sort cerebral ischemia is exacerbated by extracellular nicotinamide phosphoribosyltransferase via a non-enzymatic mechanism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877362/
https://www.ncbi.nlm.nih.gov/pubmed/24392007
http://dx.doi.org/10.1371/journal.pone.0085403
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